Rewarding effects of ethanol and cocaine in µ opioid receptor-deficient mice

Becker, Axel; Grecksch, Gisela; Kraus, Jürgen; Loh, Horace H.; Schroeder, Helmut; Höllt, Volker

doi:10.1007/s00210-002-0533-2

Cited by 117 publications

(97 citation statements)

References 59 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cocaine-induced locomotor activity has not been described previously for chronic NTX pretreated animals. With respect to m-opioid receptor knockout mice, the present findings are in agreement with those of Becker et al (2002) who also reported comparable cocaine-induced locomotor activity for m-opioid receptor knockout mice, which lack exons 2 þ 3 of the m-opioid receptor gene, and wild-type controls. Taken together, mopioid receptors are not required for the acute locomotor response to cocaine in mice.…”

Section: Acute Cocaine-induced Locomotor Activitysupporting

confidence: 92%

μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

Lesscher

Hordijk

Bondar

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

Although m-opioid receptors have been extensively investigated for their role in drug reinforcement, little is known about the contribution of these receptors to the acute and sensitized locomotor response to cocaine. In this study m-opioid receptor involvement in acute cocaine-induced locomotor activity and in the development of cocaine-induced behavioral sensitization was evaluated using mopioid receptor knockout mice and chronic naltrexone (NTX) pretreatment as models. In addition, co-administration of the specific mopioid receptor antagonist CTOP with repeated saline or cocaine injections was used to establish the involvement of m-opioid receptors in sensitization to the locomotor stimulant effects of cocaine. The acute locomotor response to cocaine (3, 10, 20, or 30 mg/kg i.p.) of mopioid receptor knockout or chronic NTX pretreated mice was not different from the cocaine response of their respective controls. With respect to cocaine-induced behavioral sensitization, induced by daily injections of 20 mg/kg cocaine for 11 subsequent days, mopioid receptor knockout mice developed behavioral sensitization to the locomotor stimulant effects of cocaine (challenge 10 mg/kg i.p.) comparable to wild-type littermates and the m-opioid receptor antagonist CTOP did not affect cocaine-induced sensitization either. However, mice that were pretreated with NTX exhibited augmented cocaine-induced behavioral sensitization relative to placebo pretreated controls, which may be ascribed to increased d-opioid receptor levels as has been described for chronic NTX pretreated mice. The present findings suggest that m-opioid receptors are not required for the acute locomotor response to cocaine nor are they essential for the development of cocaine-induced behavioral sensitization.

show abstract

Section: Acute Cocaine-induced Locomotor Activitysupporting

confidence: 92%

μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

Lesscher

Hordijk

Bondar

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Similarly, m-OR knockout mice self-administer alcohol at lower levels when compared with wild-type controls (Becker et al, 2002;Hall et al, 2001;Roberts et al, 2000). In rodents, chronic alcohol consumption has been shown to increase m-OR binding in limbic areas including the nucleus accumbens (Cowen et al, 1998(Cowen et al, , 1999Djouma and Lawrence, 2002).…”

Section: Introductionmentioning

confidence: 99%

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Weerts

Kim

Wand

et al. 2007

Neuropsychopharmacol

139

147

View full text Add to dashboard Cite

Blockade of brain m-opioid receptor (m-OR) and d-opioid receptor (d-OR) was investigated in recently abstinent alcohol-dependent subjects (N ¼ 21) maintained on naltrexone. Subjects completed a 19-day inpatient protocol, which included alcohol abstinence followed by naltrexone treatment (50 mg) on days 15-19. Blood samples were collected after the first administration of naltrexone to evaluate serum levels of naltrexone and 6-b-naltrexol. Regional brain m-OR binding potential (BP) and d-OR K i was measured using [ 11 C]carfentanil (CAR) positron emission tomography (PET) and [11 C]methyl naltrindole ([ 11 C]MeNTI) PET, respectively, before (day 5) and during naltrexone treatment (day 18). Naltrexone inhibition of [ 11 C]CAR BP was near maximal across all brain regions of interest with little variability across subjects (mean + SD% inhibition ¼ 94.9 + 4.9%). Naltrexone only partially inhibited the [ 11 C]MeNTI K i and there was more variability across subjects (mean + SD% inhibition ¼ 21.1 + 14.49%). Peak serum levels of naltrexone were positively correlated with % inhibition of d-OR K i in neocortex and basal ganglia. Peak serum levels of naltrexone were not correlated with % inhibition of m-OR BP. Peak levels of 6-b-naltrexol were not significantly correlated with % inhibition of m-OR BP or d-OR K i . Thus, the FDA recommended therapeutic dose of naltrexone was sufficient to produce near complete inhibition of the m-OR in recently abstinent alcohol dependent subjects. The lower percent inhibition of d-OR and greater variability in d-OR blockade by naltrexone across subjects may contribute to individual differences in treatment outcomes to naltrexone. Further investigations on the relationship between individual differences in d-OR blockade by naltrexone and clinical outcomes should be explored.

show abstract

“…Targeted gene mutation (knockout) strategies provided mice that lack opioid peptides or receptors. Thus, mice lacking μ-opioid receptors, generated from three distinct constructs, do not self-administer ethanol under various conditions, including oral self-administration and two-bottle choice, and do not display conditioned place preference to ethanol (Becker et al, 2002;Hall et al, 2001;Roberts et al, 2000). Surprisingly, significantly reduced ethanol consumption was also shown in mice lacking κ-opioid receptors (Kovacs et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Reduced alcohol consumption in mice lacking preprodynorphin

Blednov

Walker

Martinez

et al. 2006

Alcohol

View full text Add to dashboard Cite

Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the κ-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 hours) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest thath this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

show abstract

Rewarding effects of ethanol and cocaine in µ opioid receptor-deficient mice

Cited by 117 publications

References 59 publications

μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Reduced alcohol consumption in mice lacking preprodynorphin

Contact Info

Product

Resources

About